Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGBCKLO)

• DOT Name: Beta-centractin (ACTR1B)
• Synonyms: Actin-related protein 1B; ARP1B
• Gene Name: ACTR1B
• Related Disease:
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Hepatocellular carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Neuroblastoma
  Urinary bladder cancer
• UniProt ID: ACTY_HUMAN
• Pfam ID: PF00022
• Sequence:
  MESYDIIANQPVVIDNGSGVIKAGFAGDQIPKYCFPNYVGRPKHMRVMAGALEGDLFIGP
  KAEEHRGLLTIRYPMEHGVVRDWNDMERIWQYVYSKDQLQTFSEEHPVLLTEAPLNPSKN
  REKAAEVFFETFNVPALFISMQAVLSLYATGRTTGVVLDSGDGVTHAVPIYEGFAMPHSI
  MRVDIAGRDVSRYLRLLLRKEGVDFHTSAEFEVVRTIKERACYLSINPQKDEALETEKVQ
  YTLPDGSTLDVGPARFRAPELLFQPDLVGDESEGLHEVVAFAIHKSDMDLRRTLFANIVL
  SGGSTLFKGFGDRLLSEVKKLAPKDIKIKISAPQERLYSTWIGGSILASLDTFKKMWVSK
  KEYEEDGSRAIHRKTF
• Function: Component of a multi-subunit complex involved in microtubule based vesicle motility. It is associated with the centrosome.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Salmonella infection (hsa05132)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Genetic Variation	[2]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[2]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[2]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[2]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[1]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[6]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Beta-centractin (ACTR1B).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Beta-centractin (ACTR1B).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Beta-centractin (ACTR1B).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Beta-centractin (ACTR1B).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Beta-centractin (ACTR1B).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Beta-centractin (ACTR1B).	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Beta-centractin (ACTR1B).	[13]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Beta-centractin (ACTR1B).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Beta-centractin (ACTR1B).	[14]

References

• [1] The neurogene BTG2TIS21/PC3 is transactivated by DeltaNp73alpha via p53 specifically in neuroblastoma cells.J Cell Sci. 2005 Mar 15;118(Pt 6):1245-53. doi: 10.1242/jcs.01704. Epub 2005 Mar 1.
• [2] Association analyses identify 31 new risk loci for colorectal cancer susceptibility.Nat Commun. 2019 May 14;10(1):2154. doi: 10.1038/s41467-019-09775-w.
• [3] Down-regulation of beta-centractin might be involved in dendritic cells dysfunction and subsequent hepatocellular carcinoma immune escape: a proteomic study.J Cancer Res Clin Oncol. 2008 Feb;134(2):179-86. doi: 10.1007/s00432-007-0267-0. Epub 2007 Jul 7.
• [4] Small interfering RNA-directed targeting of Toll-like receptor 4 inhibits human prostate cancer cell invasion, survival, and tumorigenicity.Mol Immunol. 2009 Sep;46(15):2876-84. doi: 10.1016/j.molimm.2009.06.016. Epub 2009 Jul 29.
• [5] Monomeric and Dimeric (68)Ga-Labeled Bombesin Analogues for Positron Emission Tomography (PET) Imaging of Tumors Expressing Gastrin-Releasing Peptide Receptors (GRPrs).J Med Chem. 2018 Mar 8;61(5):2062-2074. doi: 10.1021/acs.jmedchem.7b01856. Epub 2018 Feb 22.
• [6] Inhibition of bladder cancer invasion by Sp1-mediated BTG2 expression via inhibition of DNA methyltransferase 1.FEBS J. 2014 Dec;281(24):5581-601. doi: 10.1111/febs.13099. Epub 2014 Oct 30.
• [7] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [13] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [14] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.